HIV IN PREGNANCY

ABSTRACT

After the 25 years since the first case of HIV/AIDS was recorded in the country, the rate of infection seems to be decreasing. 

National HIV/AIDS Strategy (2010-2016) aims to decrease HIV prevalence rate by 50 percent, AIDS related deaths by 25 percent and HIV prevalence in newborns by 90 percent, compared to the situation in 2010. 

According to latest data compiled by the National Center for AIDS and STD Control (NCASC), 1,088 new HIV cases have been reported in 2012. Altogether 1,437 cases were reported in 2011, down from 1,751 cases in 2010. Only 2,433 HIV patients have been receiving the medication provided by the government at present. It is estimated that there are 48,600 people living with HIV/AIDS virus. But, only 21,551 patients have been registered with the government. 

In 2007 : Total no. of patient infected with HIV in Nepal is estimated to be 69790 with 92% in the age group 15–49 yrs

HIV in general population < 1%

Sex ratio: 3:1 (male to female)

In 2007: 1811 women were in need of antiretroviral therapy to prevent mother to child transmission Mother to child transmission is largest source of HIV infection in children in Nepal

Out of estimated 900,000 annual pregnancy, 1800 are estimated to occur in HIV positive women (2005)

WHO estimates at least 50% of people infected with HIV are female. Majority of these women in reproductive years and elect to have children after HIV infection.

2 million HIV infected women become pregnant each year 2000 new HIV infected infants each day.



Epidemiology

Caused by RNA virus characterized by enzyme reverse transcriptase.

Allows viral RNA to be transcribed to viral DNA which is randomly incorporated into host nucleic DNA and subsequently transcribed to produce viral RNA Envelop glycoproteins confer ability for virus to attach to cells bearing CD4+ antigen (esp T- Helper lymphocytes).

Rapid and continous replication of HIV impairs and eventually depletes the patient CD4+ T cell population ----- debilitation of host immune system.

Patient susceptible to opportunistic infections and neoplasia that characterises AIDS.

During replication , mutation occur in DNA copies --- drug resistance.

Initial HIV infection may be asymptomatic.

May produce an acute glandular fever type illness associated with characteristic rash.

Antibodies detected in the serum within 3 months of infection(seroconversion).

Mean time from infection to development of AIDS is 8-10 yrs.

HIV 1: North, Central and South America, Europe and Asia.

HIV 2: West Africa.


Infection is from:

 Blood, semen , saliva, female genital tract secretion and breast milk.



Route of transmission

Sexual intercourse.

Intravenous drug use and use of infected blood and blood products.

Vertical transmission.



HIV in pregnancy

Pregnancy does not accelerate HIV disease progression HIV disease may affect the outcome of pregnancy

IUGR

Preterm birth

Low birth weight

Perinatal and neonatal death

     Does not increase the incidence of congenital anomaly.



Screening of HIV in pregnancy

WHO recommends screening when for any condition, benefits of a positive test outweigh the risks.



Early recognition of HIV disease important in pregnancy

Woman will receive optimal medical care for her condition and various strategi es can be employed to minimise risk of HIV transmission to fetus.

Woman counselled about implications of pregnancy with HIV.

           Option of pregnancy termination where appropriate.

 Pediatrician involved early in the management should woman elect to continue pregnancy.



Types of screening

Universal screening : where seroprevalence is greater.
High risk screening: low prevalence rate.
Opt in method
Opt out method

Mother to child transmission : Issue about HIV infection.

 Voluntary testing and counselling of HIV was first started in Nepal in 1995 at National Center for AIDS and STD control.

 Comprehensive PMTCT service started in Nepal from Feb 2005 at 7 different sites.
 Now there are 17 PMTCT sites in Nepal.
 In Kathmandu: TUTH and maternity hospital.



Mother to child transmission : Issue about HIV infection

Vertical transmission rate: 14% in western world.

Higher transmission rate in developing world.

Breast feeding further increase the risk by 14%.

 Management of pregnancy with HIV made difficult by fact that no practical method of prenatal diagnosis to predict which infants are affected.


Reasons :

Methods of prenatal diagnosis as cordocentesis are invasive and carry risk of infecting fetus with HIV by innoculating maternal blood.

Majority of neonatal infection occurs during delivery process so impossible to predict which neonate will be ultimately infected.
Early diagnosis of HIV infection in neonate difficult as maternal HIV IgG Ab cross the placenta and persist in fetal circulation for upto 18 months.




HIV may be transmitted to infant

During pregnancy

At the time of delivery

Through breastfeeding



Factors increasing risk of transmission:

 HIV seroconversion during pregnancy

High maternal viral load > 5-10,000 copies/ml

Advancing maternal disease(p24 antigenemia)

Malaria

Recurrent STI

Premature delivery

Rupture of membrane more than 4 hours

Vaginal delivery

Invasive procedures during delivery ( vacuum, forceps, episiotomy. Fetal scalp vein sampling)

Placental distruption

Breast feeding



  Care of pregnant women infected with HIV should be Multidisciplinary

Should involve

Obstetrician

HIV physician

General practioner

Pediatrician

Midwives

Health visitors

Social worker 



1. Counseling about implications of pregnancy with HIV disease and provide psycological support

Personal prognosis

Illicit drug use

Vertical transmission rates

No method of prenatal diagnosis

Option of pregnancy termination

Breastfeeding

2. Routine antenatal care

3. Diagnosis and aggressive treatment of malaria, STI and other infection.

4. Educate about MTCT and infant feeding option 

5.Screening and follow up tests in pregnancy


Test                                                                                      Frequency

Complete blood count                                                          3 monthly

Liver function test                                                                3 monthly

Hepatitis B and C markers                                                   baseline

Toxoplasma serology                                                           baseline

Syphilis serology                                                                  baseline

Cervical cytology                                                                 baseline/yearly

T cells                                                                                   3 monthly

P24 antigen                                                                           3 monthly


6. Invasive pre-natal diagnostic procedures should be avoided 


7. At each routine ANC visit,

Require about symptoms suggestive of HIV related infection.

Full physical examination including fundoscopy and chest auscultation performed at minimum of 3 monthly interval by HIV physician.

8. Prophylaxis against Pneumocystic pneumonia indicated if CD4 lymphocyte count falls below 200/mm3 or in women with symptomatic disease.
Cotrimoxazole 960mg/day offers protection also against toxoplasmosis.



Conduct of labor and delivery

Precautions taken to minimise the risk of nosocomial infections to healthcare workers and the risk of vertical transmission to fetus

 Double gloving

Use of water proof gowns

Wearing of spectacles


To decrease vertical transmission

Women of unknown status in labor, offer opt out testing

If not on antiretroviral therapy, give nevirapine

Avoid ARM or leave this as late as possible thereby minimizing fetal contact with maternal secretion

Do only minimal digital examination after rupture of membrane

Chorioamnionitis increase rate of vertical transmission so avoid ascending infection

Reduce use of assisted vaginal delivery

Reduce use of episiotomy

Role of elective LSCS (Lower Segment Caeserian Section)

LSCS if indicated performed by most experienced person available to reduce risk of injury to staff

Third stage conducted actively to reduce blood loss


Neonatal period

Baby should be examined by pediatrician.

Avoid mechanical nasal suction.

Clean the newborn immediately of all maternal secretion and blood.

Hematological, virological and immunological investigations should be undertaken at birth, 6 weeks and 3 monthly thereafter.

Antiretroviral therapy for infants.

Support safer infant feeding.
If breastfeeding chosen: exclusive breastfeeding,
                                advise early and rapid weaning.


 Serological and Virological tests in newborn at risk of HIV

Full blood count and differential count

T lymphocyte subset

Hepatitis B serology

HIV serology– ELISA

Virus isolation by lymphocyte culture.

PCP occur frequently in infants under 6 months so Prophylaxis with co-trimoxazole from 3 weeks of age is Recommended.

Follow up schedule discussed with parents.

Mother will require advice on immunisation.


Vaccine                                                                   Indication

Polio                                                                   Use killed vaccine

BCG                                  Withhold from children definitely known to be infected but give all others

H. Influenza                                                  All HIV infected children

Pneumococcus                                              All HIV infected children

Hepatitis B IG                                                         Within 7 days

Hepatitis B vaccine                                                 1 and 6 months

Support safer infant feeding.

If breastfeeding is chosen: Exclusive breastfeeding Rapid and early weaning.

Counselling on risks and benefit of breast feeding.



 Risk of breastfeeding in HIV infected mothers


HIV infection

Infection risk persists for length of breastfeeding

 Children who receive mixed feeding are at increased risk of HIV infection than children who receive exclusive breastfeeding or exclusive replacement feeding

Shortening the period of breastfeeding may reduce the risk of HIV transmission.

The alternative of exclusively giving replacement feeding also has considerable risks

Studies show that replacement fed babies are 2.5 to 5 times more likely to die from any cause than breast fed babies.



Benefits of breastfeeding in HIV infected mothers 


The immunological, nutritional, psychosocial, and child-spacing benefits are well recognized.

Breast milk plays an important role in preventing the infections that accelerate progression of HIV-related diseases in already infected children.



Nepal PMTCT guidelines on breastfeeding 


When replacement feeding is acceptable, feasible, affordable, sustainable and safe, avoid all breastfeeding in women who are HIV positive.

Otherwise exclusive breastfeeding for 6 months.

Avoid mix feeding as formula feed increase G.I. tract inflammation and allows virus to enter infant blood stream easily.

As soon as feasible, discontinue breastfeeding.

Counselling on pros and cons of breastfeeding.



Antiretroviral therapy (ART)

Drugs used to treat HIV infection impair viral replication so delay immunodeficiency and progression to AIDS .Drugs used in pregnancy :

Zidovudine

Nevirapine

ART in pregnancy aims to prevent vertical transmission and maintain maternal health.


Risks : 

Feto-maternal exposure with potential adverse effects.

Emergence of resistent viral strain.

Recommended optimal time to initiate therapy in late 3rd Trimester since less than 2% of mother to infant transmission occur before 3rd trimester.

Role of single agent (monotherapy).



Zidovudine 

100mg orally five times per day from 34 weeks antenatally

2mg/kg body weight i/v for one hour in labor followed by 1mg/kg/hour until delivery

2mg/kg orally every 6 hours for 6 weeks for neonate beginning 8-12 hours after birth

Rate of vertical transmission is reduced by 67% (placebo 25.5% vs AZT 8.3%)


Nevirapine

Nevirapine another single agent used.

200mg Nevirapine at onset of labor.

Single dose 2mg/kg Nevirapine for neonate within 3 days of Delivery.

Relatively cheap, easy to administer and used in developing countries.

Reduce the risk of transmission by 47%.



Pitfall of single dose Nevirapine course


Concerns of resistance with single dose NVP and the future effect on maternal ART efficacy are currently being addressed in trials.

WHO recommendations:

continue with sd NVP prophylaxis programs for now because of potential for huge number of infant infections avoided

await trial results



Combination therapy 


Triple therapy indicated for pregnant women with :

Advanced HIV disease.

High viral load.

Low CD4+ counts.

Since risk of MTCT correlates with these parameters.



Nepal PMTCT (Prevention of mother to child transmission) ARV prophylaxis

Intrapartum short course: Nevirapine 200mg orally at labor onset

Postpartum infant: Nevirapine 2mg/kg oral suspension immediately after birth.


In case mother received no ARV prophylaxis:

•Postpartum infant: Nevirapine 2mg/kg immediately after birth and Zidovudine 4mg/kg twice daily for 7 days.

•If Zidovudine not available : give immediate NVP dose and 2nd dose 72 hours after birth.